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Neuronal Properties and Synaptic Connectivity in Rodent Presubiculum Jean Simonnet

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Neuronal Properties and Synaptic Connectivity in Rodent Presubiculum Jean Simonnet Neuronal properties and synaptic connectivity in rodent presubiculum Jean Simonnet To cite this version: Jean Simonnet. Neuronal properties and synaptic connectivity in rodent presubiculum. Neurons and Cognition [q-bio.NC]. Université Pierre et Marie Curie - Paris VI, 2014. English. NNT : 2014PA066435. tel-02295014 HAL Id: tel-02295014 https://tel.archives-ouvertes.fr/tel-02295014 Submitted on 24 Sep 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. THÈSE DE DOCTORAT DE L’UNIVERSITÉ PIERRE ET MARIE CURIE Spécialité Neurosciences École doctorale Cerveau – Cognition – Comportement Présentée par : Jean Simonnet Pour obtenir le grade de DOCTEUR DE L’UNIVERSITÉ PIERRE ET MARIE CURIE Sujet de la thèse : Neuronal properties and synaptic connectivity in rodent presubiculum Soutenue le 23.09.2014 devant le jury composé de : Dr Jean-Christophe Poncer Président Dr Dominique Debanne Rapporteur Dr Maria Cecilia Angulo Rapportrice Pr Hannah Monyer Examinatrice Dr Bruno Cauli Examinateur Dr Desdemona Fricker Directrice de thèse Université Pierre & Marie Curie - Paris 6 Tél. Secrétariat : 01 42 34 68 35 Bureau d’accueil, inscription des doctorants Fax : 01 42 34 68 40 et base de données Tél. pour les étudiants de A à EL : 01 42 34 68 41 Esc. G, 2ème étage Tél. pour les étudiants de EM à MON : 01 42 34 68 41 15 Rue de l’école de médecine Tél. pour les étudiants de MOO à Z : 01 42 34 68 51 75270 - PARIS CEDEX 06 E-mail : [email protected] Abstract Cognitive functions rely on the generation and regulation of information in special- ized neuronal networks. The presubiculum, a cortical area located between the hip- pocampus and the entorhinal cortex, is involved in signaling the sense of orientation in animals as well as in humans. Most presubicular neurons are Head Direction Cells, that is, they fire as a function of directional heading. The presubiculum constitutes a crucial crossroad for spatial information. Very few data exist on the functional organization of the presubiculum, but its 6-layered cytoarchitecture suggests that signals are not passively relayed but rather actively integrated and refined. During my PhD, I studied the microcircuit elements of rodent presubiculum in the slice preparation, linking structure and physiology using patch clamp records. First, I focused on rat principal neurons and distinguished 3 groups: a homoge- neous population of regular spiking neurons in superficial layers, mostly pyramidal; intrinsically burst firing neurons of layer 4; and a very heterogeneous population of regular spiking neurons in deep layers. These populations constitute the primary el- ements for information processing in the presubiculum, and their diversity suggests a high computational power. Then, I addressed the question of the inhibitory control in the presubiculum. Recordings were performed from slices of transgenic mouse strains that express fluo- rescent proteins in interneurons. We showed a continuum of diversity for parvalbumin- (PV) and somatostatin- (SST) containing interneurons, from the archetypical PV- positive fast spiking basket cells to the SST-positive low-threshold spiking Martinotti cells. Regarding the inhibition, the presubiculum seems to possess the complexity of all cortical areas. Finally, I investigated the synaptic interactions of pyramidal cells and Martinotti cells in superficial layers, using dual patch clamp recordings. Martinotti cells provide low amplitude but reliable inhibition onto pyramidal cell dendrites. I found that the strength at the excitatory synapse was enhanced following repetitive stimulation at high frequency. Consequently, dendritic inhibition by presubicular Martinotti cells may act as a homeostatic response to sustained excitation. My PhD work brought essential knowledge about the presubicular microcircuit. It has shed light on the different populations of principal neurons and GABAergic interneurons and has uncovered a feedback inhibitory loop that is recruited during sustained but not transient activity. Acknowledgments First, I would like to thank the members of my Jury: Hannah Monyer, Jean Christophe Poncer, Bruno Cauli as well as Dominique Debanne and Maria Cecilia Angulo who have accepted to review this manuscript. Je tiens à remercier Desdemona, qui m’a donné l’opportunité de travailler avec elle et qui m’a encadré tout au long de cette thèse. Tu as su me donner la liberté de travail dont j’avais besoin, et je te remercie de m’avoir permis d’exprimer mes idées et mes envies tout en ayant un oeil critique et avisé à chaque étape. Je pense que cela n’a pas été une chose facile avec mon caractère plutôt ombrageux. Difficile à convaincre notamment. Disons que nous avons eu un certain nombre de discussions passionnées sur la « bonne manip à faire » ou « la figure à montrer » ou « ce qu’il faut dire ». J’ai toujours pris cela dans le sens positif, à savoir que la confronta- tion de nos idées a toujours permis d’améliorer notre travail. Je voudrais aussi te remercier pour la compréhension dont tu as fait preuve, par rapport aux aléas de la vie qui ne concernent en rien le travail, mais qui l’impactent inévitablement. Enfin, je souhaite exprimer toute ma gratitude de m’avoir toujours soutenu tout au long de ces années. Bien évidemment, cette thèse ne serait pas possible sans Richard, qui m’a ouvert les portes de son laboratoire et apporté son soutien quotidien. Vous avez su me prodiguer de très bons conseils durant toute cette thèse. S’il y a une chose que j’ai appris, c’est bien qu’un message simple est beaucoup plus fort. Faire des figures simples, des diapos simples, écrire des phrases courtes. « More is less ». Je tiens également à vous remercier de m’avoir toujours valorisé auprès de vos pairs. Merci à tous les membres de l’équipe. Emmanuel, Michael, Ivan, Lim-Anna, Con- stanze, Roxanne, Caroline, Maja, Etienne, Juliane, Katia, Bertrand et Mérie. Vous m’avez tous beaucoup apporté sur le plan scientifique et humain. Je pense à Em- manuel qui m’a appris tout ce qu’il savait sur l’imagerie structurée ou l’immunohisto- chimie. Je pense à Caroline qui m’a beaucoup conseillé pour les doubles enreg- istrements. Je me rappelle du temps passé devant le poste d’enregistrement de Michael à regardé défiler les enregistrements. Je pense aussi aux bons moments passés autour d’une bière, ou lors des dégustations de vin. Une spéciale pour Mérie qui prend la relève auprès de Desdemona, et qui a du me supporter pendant cette dernière année, j’avoue que je n’ai pas toujours été très tendre et surement trop exigent parfois. Merci à Alberto et toute son équipe avec qui j’ai souvent interagi pour résoudre mes problèmes de souris, de tranches, de solution intra, ou d’oxygène. Je dois avoir une dette de café envers Charlotte qu’il faudra régler un de ces jours. Merci à Claire et Stéphane ainsi qu’à leurs équipes, avec qui j’ai peut être moins interagi, mais qui ont apporté leur petit grain de sel de temps à autre. Merci à Sean. Sean tu venais au labo pour travailler avec Desdemona et c’est vrai que nous discutions souvent de tes manips et j’ai pu t’aider de temps à autre quand tu avais des problèmes. Un jour, tu m’as simplement proposé de participer active- ment à ton projet. J’en ai été très touché. Cette collaboration m’a également permis d’améliorer mon anglais et tu as été très pédagogue de ce point de vue là. Merci à l’animalerie du 105, de l’ICM, aux plateformes de génotypage et d’histologie pour leur aide et support technique. Merci aux Ajités. William, Pinar, Morgane P, Fabian, Kevin, Tristan, Morgane B, Alizée, . Je ne peux pas citer tous les noms, mais ils sauront se reconnaitre. On a passé de très bons moments tous ensemble et belle dynamique a été créée à l’ICM. Continuez s’il vous plait ! Je souhaite remercier Patricia Oliviero qui a superbement organisé, avec moi, la retraite des Doc et PostDoc en 2013. Merci pour toutes les petites choses que tu as faites pour moi, ne change rien tu es géniale ! Merci à la promo de master/thèse et associés. Carole, Audrey, Patrick, Esther, Nico, Raphael, Béné, Isa. j’en oublie c’est sur. On a passé de très bons moments, sou- vent de détente il faut le reconnaître, mais cela a été important pour tenir tout au long de ces années. Carole. On était à la fac à Orléans en licence, on est venu à Paris avec la ferme intention de faire une thèse en neuro. On peut dire que c’est mission accomplie. Je pense que ca aurait été plus difficile sans toi sur le plan moral. Tu as su ètre présente au moment ou j’en avais besoin. Mème si l’on a fait des choses très différentes lors de nos thèses, nos discussions scientifiques m’ont aussi beaucoup apportées. Merci à Y. Audrey. On travaillait sur des modèles similaires, avec les mèmes prob- lèmes. Enfin j’avais les problèmes, tu avais les solutions. Je suis venu te voir à plusieurs reprises quand j’avais des soucis de tranches ou de stéréotaxie, et tu as toujours été d’une aide plus que précieuse. Je pense que tu m’as aussi beaucoup influencé, sans que je ne me rende vraiment compte, dans ma façon de travailler.
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